The Experts below are selected from a list of 159 Experts worldwide ranked by ideXlab platform
Li Yen Mae Huang - One of the best experts on this subject based on the ideXlab platform.
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P2X7 receptors in Satellite Glial Cells mediate high functional expression of P2X3 receptors in immature dorsal root ganglion neurons
Molecular pain, 2012Co-Authors: Yong Chen, Li Yen Mae HuangAbstract:Background The purinergic P2X3 receptor (P2X3R) expressed in the dorsal root ganglion (DRG) sensory neuron and the P2X7 receptor (P2X7R) expressed in the surrounding Satellite Glial Cell (SGC) are two major receptors participating in neuron-SGC communication in adult DRGs. Activation of P2X7Rs was found to tonically reduce the expression of P2X3Rs in DRGs, thus inhibiting the abnormal pain behaviors in adult rats. P2X receptors are also actively involved in sensory signaling in developing rodents. However, very little is known about the developmental change of P2X7Rs in DRGs and the interaction between P2X7Rs and P2X3Rs in those animals. We therefore examined the expression of P2X3Rs and P2X7Rs in postnatal rats and determined if P2X7R-P2X3R control exists in developing rats.
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Neuronal soma–Satellite Glial Cell interactions in sensory ganglia and the participation of purinergic receptors
Neuron glia biology, 2010Co-Authors: Yong Chen, Congying Wang, Xiaofei Zhang, Li Yen Mae HuangAbstract:It has been known for some time that the somata of neurons in sensory ganglia respond to electrical or chemical stimulation and release transmitters in a Ca2+-dependent manner. The function of the somatic release has not been well delineated. A unique characteristic of the ganglia is that each neuronal soma is tightly enwrapped by Satellite Glial Cells (SGCs). The somatic membrane of a sensory neuron rarely makes synaptic contact with another neuron. As a result, the influence of somatic release on the activity of adjacent neurons is likely to be indirect and/or slow. Recent studies of neuron-SGC interactions have demonstrated that ATP released from the somata of dorsal root ganglion neurons activates SGCs. They in turn exert complex excitatory and inhibitory modulation of neuronal activity. Thus, SGCs are actively involved in the processing of afferent information. In this review, we summarize our understanding of bidirectional communication between neuronal somata and SGCs in sensory ganglia and its possible role in afferent signaling under normal and injurious conditions. The participation of purinergic receptors is emphasized because of their dominant roles in the communication.
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neuronal soma Satellite Glial Cell interactions in sensory ganglia and the participation of purinergic receptors
Neuron Glia Biology, 2010Co-Authors: Yong Chen, Congying Wang, Xiaofei Zhang, Li Yen Mae HuangAbstract:It has been known for some time that the somata of neurons in sensory ganglia respond to electrical or chemical stimulation and release transmitters in a Ca2+-dependent manner. The function of the somatic release has not been well delineated. A unique characteristic of the ganglia is that each neuronal soma is tightly enwrapped by Satellite Glial Cells (SGCs). The somatic membrane of a sensory neuron rarely makes synaptic contact with another neuron. As a result, the influence of somatic release on the activity of adjacent neurons is likely to be indirect and/or slow. Recent studies of neuron-SGC interactions have demonstrated that ATP released from the somata of dorsal root ganglion neurons activates SGCs. They in turn exert complex excitatory and inhibitory modulation of neuronal activity. Thus, SGCs are actively involved in the processing of afferent information. In this review, we summarize our understanding of bidirectional communication between neuronal somata and SGCs in sensory ganglia and its possible role in afferent signaling under normal and injurious conditions. The participation of purinergic receptors is emphasized because of their dominant roles in the communication.
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neuronal somatic atp release triggers neuron Satellite Glial Cell communication in dorsal root ganglia
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Xiaoli Zhang, Yuhong Chen, Congying Wang, Li Yen Mae HuangAbstract:It has been generally assumed that the Cell body (soma) of a neuron, which contains the nucleus, is mainly responsible for synthesis of macromolecules and has a limited role in Cell-to-Cell communication. Using sniffer patch recordings, we show here that electrical stimulation of dorsal root ganglion (DRG) neurons elicits robust vesicular ATP release from their somata. The rate of release events increases with the frequency of nerve stimulation; external Ca2+ entry is required for the release. FM1–43 photoconversion analysis further reveals that small clear vesicles participate in exocytosis. In addition, the released ATP activates P2X7 receptors in Satellite Cells that enwrap each DRG neuron and triggers the communication between neuronal somata and Glial Cells. Blocking L-type Ca2+ channels completely eliminates the neuron–glia communication. We further show that activation of P2X7 receptors can lead to the release of tumor necrosis factor-α (TNFα) from Satellite Cells. TNFα in turn potentiates the P2X3 receptor-mediated responses and increases the excitability of DRG neurons. This study provides strong evidence that somata of DRG neurons actively release transmitters and play a crucial role in bidirectional communication between neurons and surrounding Satellite Glial Cells. These results also suggest that, contrary to the conventional view, neuronal somata have a significant role in Cell–Cell signaling.
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Neuronal somatic ATP release triggers neuron–Satellite Glial Cell communication in dorsal root ganglia
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Xiaoli Zhang, Yuhong Chen, Congying Wang, Li Yen Mae HuangAbstract:It has been generally assumed that the Cell body (soma) of a neuron, which contains the nucleus, is mainly responsible for synthesis of macromolecules and has a limited role in Cell-to-Cell communication. Using sniffer patch recordings, we show here that electrical stimulation of dorsal root ganglion (DRG) neurons elicits robust vesicular ATP release from their somata. The rate of release events increases with the frequency of nerve stimulation; external Ca2+ entry is required for the release. FM1–43 photoconversion analysis further reveals that small clear vesicles participate in exocytosis. In addition, the released ATP activates P2X7 receptors in Satellite Cells that enwrap each DRG neuron and triggers the communication between neuronal somata and Glial Cells. Blocking L-type Ca2+ channels completely eliminates the neuron–glia communication. We further show that activation of P2X7 receptors can lead to the release of tumor necrosis factor-α (TNFα) from Satellite Cells. TNFα in turn potentiates the P2X3 receptor-mediated responses and increases the excitability of DRG neurons. This study provides strong evidence that somata of DRG neurons actively release transmitters and play a crucial role in bidirectional communication between neurons and surrounding Satellite Glial Cells. These results also suggest that, contrary to the conventional view, neuronal somata have a significant role in Cell–Cell signaling.
Elise F Stanley - One of the best experts on this subject based on the ideXlab platform.
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low voltage activated calcium channels gate transmitter release at the dorsal root ganglion sandwich synapse
The Journal of Physiology, 2013Co-Authors: Gabriela M Rozanski, Arup R Nath, Michael E Adams, Elise F StanleyAbstract:Key points • Sensory neurons in dorsal root ganglia (DRG) lack direct inter-somatic synaptic contacts but a subpopulation can communicate with their immediate neighbours via transGlial, neuron–Glial Cell–neuron ‘sandwich synapses’. • We used gently dissociated chick DRG to explore the properties and identity of the voltage sensitive calcium channel responsible for gating transmitter (ATP) release at the neuron-to-Glial Cell synapse. • A combined pharmacological and biophysical characterization identified the T type, CaV3.2 calcium channel. • The low voltage-activated and inactivation-sensitive properties of CaV3.2 suggest that sandwich synapse transmission is gated not only by action potentials but also by sub-threshold membrane depolarizations. • CaV3.2 modulating agents are of interest as anaesthetics, raising the possibility that sandwich synapse transmission plays a role in the aetiology of DRG-derived abnormal sensation and pain. Abstract A subpopulation of dorsal root ganglion (DRG) neurons are intimately attached in pairs and separated solely by thin Satellite Glial Cell membrane septa. Stimulation of one neuron leads to transGlial activation of its pair by a bi-, purinergic/glutamatergic synaptic pathway, a transmission mechanism that we term sandwich synapse (SS) transmission. Release of ATP from the stimulated neuron can be attributed to a classical mechanism involving Ca2+ entry via voltage-gated calcium channels (CaV) but via an unknown channel type. Specific blockers and toxins ruled out CaV1, 2.1 and 2.2. Transmission was, however, blocked by a moderate depolarization (−50 mV) or low-concentration Ni2+ (0.1 mm). Transmission persisted using a voltage pulse to −40 mV from a holding potential of −80 mV, confirming the involvement of a low voltage-activated channel type and limiting the candidate channel type to either CaV3.2 or a subpopulation of inactivation- and Ni2+-sensitive CaV2.3 channels. Resistance of the neuron calcium current and SS transmission to SNX482 argue against the latter. Hence, we conclude that inter-somatic transmission at the DRG SS is gated by CaV3.2 type calcium channels. The use of CaV3 family channels to gate transmission has important implications for the biological function of the DRG SS as information transfer would be predicted to occur not only in response to action potentials but also to sub-threshold membrane voltage oscillations. Thus, the SS synapse may serve as a homeostatic signalling mechanism between select neurons in the DRG and could play a role in abnormal sensation such as neuropathic pain.
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transGlial transmission at the dorsal root ganglion sandwich synapse Glial Cell to postsynaptic neuron communication
European Journal of Neuroscience, 2013Co-Authors: Gabriela M Rozanski, Qi Li, Elise F StanleyAbstract:: The dorsal root ganglion (DRG) contains a subset of closely-apposed neuronal somata (NS) separated solely by a thin Satellite Glial Cell (SGC) membrane septum to form an NS-Glial Cell-NS trimer. We recently reported that stimulation of one NS with an impulse train triggers a delayed, noisy and long-lasting response in its NS pair via a transGlial signaling pathway that we term a 'sandwich synapse' (SS). Transmission could be unidirectional or bidirectional and facilitated in response to a second stimulus train. We have shown that in chick or rat SS the NS-to-SGC leg of the two-synapse pathway is purinergic via P2Y2 receptors but the second SGC-to-NS synapse mechanism remained unknown. A noisy evoked current in the target neuron, a reversal potential close to 0 mV, and insensitivity to calcium scavengers or G protein block favored an ionotropic postsynaptic receptor. Selective block by D-2-amino-5-phosphonopentanoate (AP5) implicated glutamatergic transmission via N-methyl-d-aspartate receptors. This agent also blocked NS responses evoked by puff of UTP, a P2Y2 agonist, directly onto the SGC Cell, confirming its action at the second synapse of the SS transmission pathway. The N-methyl-d-aspartate receptor NR2B subunit was implicated by block of transmission with ifenprodil and by its immunocytochemical localization to the NS membrane, abutting the Glial septum P2Y2 receptor. Isolated DRG Cell clusters exhibited daisy-chain and branching NS-Glial Cell-NS contacts, suggestive of a network organization within the ganglion. The identification of the Glial-to-neuron transmitter and receptor combination provides further support for transGlial transmission and completes the DRG SS molecular transmission pathway.
Paul L. Durham - One of the best experts on this subject based on the ideXlab platform.
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Tonabersat Inhibits Trigeminal Ganglion Neuronal‐Satellite Glial Cell Signaling
Headache, 2009Co-Authors: Srikanth Damodaram, Srikanth Thalakoti, Stacy E. Freeman, Filip G. Garrett, Paul L. DurhamAbstract:Migraine patients often report sinus pressure or pain and nasal congestion during severe migraine attacks and it has been suggested that sinus pathology can act as a trigger of migraine.1,2 Furthermore, patients suffering from acute allergic rhinitis experience headache and migraine at a much higher frequency than nonallergic subjects.3 While migraine and rhinosinusitis exhibit considerable comorbidity, the underlying Cellular mechanisms are not well understood. However, it is well established that activation of trigeminal nerves and the peripheral and central release of neuropeptides are involved in mediating the inflammatory and nociceptive events characteristic of both migraine and rhinosinusitis.4–6 The trigeminal nerve consists of 3 major branches referred to as the ophthalmic (V1), maxillary (V2), and mandibular (V3) branches. Each branch provides somatosensory innervation of distinct regions of the head, face, nasal, and sinus cavities.7 Primary afferent neurons, whose Cell bodies reside in the trigeminal ganglion, convey sensory information from peripheral tissues implicated in migraine and rhinosinusitis to the central nervous system (CNS). The pathophysiological events involved in migraine and rhinosinusitis involve both peripheral and central sensitization.4,8–10 Peripheral sensitization, which is the result of increased activity of trigeminal nociceptors, is thought to play a key role in the initiation of migraine and rhinosinusitis, while central sensitization, which involves enhanced excitability of second-order neurons, leads to pain.11 Peripheral sensitization is characterized by increased neuronal excitability and a lowering of the threshold for activation. In this context, activation is defined as causing changes in the Cell that allow it to perform functions beyond those present in a basal state.12 It is now thought that glia Cells that are closely associated with peripheral and central neurons can directly modulate the functional and excitability state of these neurons.12,13 Furthermore, neuronglia interactions are reported to be involved in all stages of inflammation and pain associated with several CNS diseases.14,15 Within the trigeminal ganglion, the Cell bodies of neurons are completely surrounded by specialized Glial Cells known as Satellite glia that together form distinct, functional units.13 Morphological studies have provided evidence that neurons and Satellite Glial Cells extend processes that are thought to facilitate exchange of chemicals between neurons and glia.16,17 In addition, it was recently shown that trigeminal ganglion neurons and Satellite Glial Cells can communicate directly via gap junctions.18 Gap junctions serve as interCellular conduits that allow for direct transfer of small molecular weight molecules, such as ions, that regulate Cellular excitability, metabolic precursors, and second messengers.19,20 Gap junctions are found in most neurons and Glial Cells and function to facilitate neuron-neuron, glia-glia, and neuron-glia communication. Within the CNS, gap junctions are abundant and allow for extensive interCellular coupling between Cells that form a communication network.19,21 Each Cell contributes a hemichannel composed of 6 transmembrane proteins known as connexins. The connexin family includes more than 20 members.22 However, only 10 connexin proteins are known to be expressed by neuronal or Glial Cells.21 Connexins are dynamic membrane proteins that exhibit short half-lives.23 Changes in the expression of connexins and hence, communication through gap junctions, are associated with numerous CNS diseases including Alzheimer’s disease, as well as cortical spreading depression.19 Similarly, we have recently provided evidence of enhanced neuron to Satellite glia communication occurring through gap junctions within trigeminal ganglion in response to inflammatory stimuli.18 The expression of connexin proteins involved in forming gap junctions between neuronal and Satellite Glial Cells within the trigeminal ganglion under normal and disease states is not known. In addition, we have observed cross activation within the ganglion by which stimulation of neurons in one branch caused a rapid and sustained activation in the other branches, an example of intraganglionic communication.18 Based on our previous findings, we propose that neuronal-Satellite Glial Cell signaling is involved in initiating and maintaining peripheral sensitization within the ganglion and, thus, contributes to the significant comorbidity reported for migraine, acute sinusitis, and allergic rhinitis. In this study, we used an in vivo animal model to test whether treatment of V2 neurons by tumor necrosis factor-alpha (TNF-α), a cytokine whose levels are elevated in nasal secretions during allergic rhinitis, can reduce the amount of stimulus required for Cellular changes in neurons located in the V1 region, and thus act as a potential trigger. Increased neuron-Satellite glia communication via gap junctions, as well as increased levels of connexin 26 and active p38, was observed in neurons and glia located in both V1 and V2 regions in response to cotreatment with TNF-α and capsaicin. Another significant finding from our study was that pretreatment with the anti-migraine drug tonabersat decreased gap junction communication and the level of connexin 26, and blocked p38 activation in both neurons and Satellite glia.
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tonabersat inhibits trigeminal ganglion neuronal Satellite Glial Cell signaling
Headache, 2009Co-Authors: Srikanth Damodaram, Srikanth Thalakoti, Stacy E. Freeman, Filip G. Garrett, Paul L. DurhamAbstract:Migraine patients often report sinus pressure or pain and nasal congestion during severe migraine attacks and it has been suggested that sinus pathology can act as a trigger of migraine.1,2 Furthermore, patients suffering from acute allergic rhinitis experience headache and migraine at a much higher frequency than nonallergic subjects.3 While migraine and rhinosinusitis exhibit considerable comorbidity, the underlying Cellular mechanisms are not well understood. However, it is well established that activation of trigeminal nerves and the peripheral and central release of neuropeptides are involved in mediating the inflammatory and nociceptive events characteristic of both migraine and rhinosinusitis.4–6 The trigeminal nerve consists of 3 major branches referred to as the ophthalmic (V1), maxillary (V2), and mandibular (V3) branches. Each branch provides somatosensory innervation of distinct regions of the head, face, nasal, and sinus cavities.7 Primary afferent neurons, whose Cell bodies reside in the trigeminal ganglion, convey sensory information from peripheral tissues implicated in migraine and rhinosinusitis to the central nervous system (CNS). The pathophysiological events involved in migraine and rhinosinusitis involve both peripheral and central sensitization.4,8–10 Peripheral sensitization, which is the result of increased activity of trigeminal nociceptors, is thought to play a key role in the initiation of migraine and rhinosinusitis, while central sensitization, which involves enhanced excitability of second-order neurons, leads to pain.11 Peripheral sensitization is characterized by increased neuronal excitability and a lowering of the threshold for activation. In this context, activation is defined as causing changes in the Cell that allow it to perform functions beyond those present in a basal state.12 It is now thought that glia Cells that are closely associated with peripheral and central neurons can directly modulate the functional and excitability state of these neurons.12,13 Furthermore, neuronglia interactions are reported to be involved in all stages of inflammation and pain associated with several CNS diseases.14,15 Within the trigeminal ganglion, the Cell bodies of neurons are completely surrounded by specialized Glial Cells known as Satellite glia that together form distinct, functional units.13 Morphological studies have provided evidence that neurons and Satellite Glial Cells extend processes that are thought to facilitate exchange of chemicals between neurons and glia.16,17 In addition, it was recently shown that trigeminal ganglion neurons and Satellite Glial Cells can communicate directly via gap junctions.18 Gap junctions serve as interCellular conduits that allow for direct transfer of small molecular weight molecules, such as ions, that regulate Cellular excitability, metabolic precursors, and second messengers.19,20 Gap junctions are found in most neurons and Glial Cells and function to facilitate neuron-neuron, glia-glia, and neuron-glia communication. Within the CNS, gap junctions are abundant and allow for extensive interCellular coupling between Cells that form a communication network.19,21 Each Cell contributes a hemichannel composed of 6 transmembrane proteins known as connexins. The connexin family includes more than 20 members.22 However, only 10 connexin proteins are known to be expressed by neuronal or Glial Cells.21 Connexins are dynamic membrane proteins that exhibit short half-lives.23 Changes in the expression of connexins and hence, communication through gap junctions, are associated with numerous CNS diseases including Alzheimer’s disease, as well as cortical spreading depression.19 Similarly, we have recently provided evidence of enhanced neuron to Satellite glia communication occurring through gap junctions within trigeminal ganglion in response to inflammatory stimuli.18 The expression of connexin proteins involved in forming gap junctions between neuronal and Satellite Glial Cells within the trigeminal ganglion under normal and disease states is not known. In addition, we have observed cross activation within the ganglion by which stimulation of neurons in one branch caused a rapid and sustained activation in the other branches, an example of intraganglionic communication.18 Based on our previous findings, we propose that neuronal-Satellite Glial Cell signaling is involved in initiating and maintaining peripheral sensitization within the ganglion and, thus, contributes to the significant comorbidity reported for migraine, acute sinusitis, and allergic rhinitis. In this study, we used an in vivo animal model to test whether treatment of V2 neurons by tumor necrosis factor-alpha (TNF-α), a cytokine whose levels are elevated in nasal secretions during allergic rhinitis, can reduce the amount of stimulus required for Cellular changes in neurons located in the V1 region, and thus act as a potential trigger. Increased neuron-Satellite glia communication via gap junctions, as well as increased levels of connexin 26 and active p38, was observed in neurons and glia located in both V1 and V2 regions in response to cotreatment with TNF-α and capsaicin. Another significant finding from our study was that pretreatment with the anti-migraine drug tonabersat decreased gap junction communication and the level of connexin 26, and blocked p38 activation in both neurons and Satellite glia.
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Nitric oxide-proton stimulation of trigeminal ganglion neurons increases mitogen-activated protein kinase and phosphatase expression in neurons and Satellite Glial Cells.
Neuroscience, 2008Co-Authors: Stacy E. Freeman, Vinit V. Patil, Paul L. DurhamAbstract:Elevated nitric oxide (NO) and proton levels in synovial fluid are implicated in joint pathology. However, signaling pathways stimulated by these molecules that mediate inflammation and pain in the temporomandibular joint (TMJ) have not been investigated. The goal of this study was to determine the effect of NO-proton stimulation of rat trigeminal neurons on the in vivo expression of mitogen-activated protein kinases (MAPKs) and phosphatases (MKPs) in trigeminal ganglion neurons and Satellite Glial Cells. Low levels of the active MAPKs extraCellular signal-regulated kinase (ERK), Jun amino-terminal kinase (JNK), and p38 were localized in the cytosol of neurons and Satellite Glial Cells in unstimulated animals. However, increased levels of active ERK and p38, but not JNK, were detected in the cytosol and nucleus of V3 neurons and Satellite Glial Cells 15 min and 2 h following bilateral TMJ injections of an NO donor diluted in pH 5.5 medium. While ERK levels returned to near basal levels 24 h after stimulation, p38 levels remained significantly elevated. In contrast to MKP-2 and MKP-3 levels that were barely detectable in neurons or Satellite Glial Cells, MKP-1 staining was readily observed in Satellite Glial Cells in ganglia from unstimulated animals. However, neuronal and Satellite Glial Cell staining for MKP-1, MKP-2, and MKP-3 was significantly increased in response to NO-protons. Increased active ERK and p38 levels as well as elevated MKP levels were also detected in neurons and Satellite Glial Cells located in V2 and V1 regions of the ganglion. Our data provide evidence that NO-proton stimulation of V3 neurons results in temporal and spatial changes in expression of active ERK and p38 and MKPs in all regions of the ganglion. We propose that in trigeminal ganglia these Cellular events, which are involved in peripheral sensitization as well as control of inflammatory and nociceptive responses, may play a role in TMJ pathology.
Gabriela M Rozanski - One of the best experts on this subject based on the ideXlab platform.
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low voltage activated calcium channels gate transmitter release at the dorsal root ganglion sandwich synapse
The Journal of Physiology, 2013Co-Authors: Gabriela M Rozanski, Arup R Nath, Michael E Adams, Elise F StanleyAbstract:Key points • Sensory neurons in dorsal root ganglia (DRG) lack direct inter-somatic synaptic contacts but a subpopulation can communicate with their immediate neighbours via transGlial, neuron–Glial Cell–neuron ‘sandwich synapses’. • We used gently dissociated chick DRG to explore the properties and identity of the voltage sensitive calcium channel responsible for gating transmitter (ATP) release at the neuron-to-Glial Cell synapse. • A combined pharmacological and biophysical characterization identified the T type, CaV3.2 calcium channel. • The low voltage-activated and inactivation-sensitive properties of CaV3.2 suggest that sandwich synapse transmission is gated not only by action potentials but also by sub-threshold membrane depolarizations. • CaV3.2 modulating agents are of interest as anaesthetics, raising the possibility that sandwich synapse transmission plays a role in the aetiology of DRG-derived abnormal sensation and pain. Abstract A subpopulation of dorsal root ganglion (DRG) neurons are intimately attached in pairs and separated solely by thin Satellite Glial Cell membrane septa. Stimulation of one neuron leads to transGlial activation of its pair by a bi-, purinergic/glutamatergic synaptic pathway, a transmission mechanism that we term sandwich synapse (SS) transmission. Release of ATP from the stimulated neuron can be attributed to a classical mechanism involving Ca2+ entry via voltage-gated calcium channels (CaV) but via an unknown channel type. Specific blockers and toxins ruled out CaV1, 2.1 and 2.2. Transmission was, however, blocked by a moderate depolarization (−50 mV) or low-concentration Ni2+ (0.1 mm). Transmission persisted using a voltage pulse to −40 mV from a holding potential of −80 mV, confirming the involvement of a low voltage-activated channel type and limiting the candidate channel type to either CaV3.2 or a subpopulation of inactivation- and Ni2+-sensitive CaV2.3 channels. Resistance of the neuron calcium current and SS transmission to SNX482 argue against the latter. Hence, we conclude that inter-somatic transmission at the DRG SS is gated by CaV3.2 type calcium channels. The use of CaV3 family channels to gate transmission has important implications for the biological function of the DRG SS as information transfer would be predicted to occur not only in response to action potentials but also to sub-threshold membrane voltage oscillations. Thus, the SS synapse may serve as a homeostatic signalling mechanism between select neurons in the DRG and could play a role in abnormal sensation such as neuropathic pain.
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transGlial transmission at the dorsal root ganglion sandwich synapse Glial Cell to postsynaptic neuron communication
European Journal of Neuroscience, 2013Co-Authors: Gabriela M Rozanski, Qi Li, Elise F StanleyAbstract:: The dorsal root ganglion (DRG) contains a subset of closely-apposed neuronal somata (NS) separated solely by a thin Satellite Glial Cell (SGC) membrane septum to form an NS-Glial Cell-NS trimer. We recently reported that stimulation of one NS with an impulse train triggers a delayed, noisy and long-lasting response in its NS pair via a transGlial signaling pathway that we term a 'sandwich synapse' (SS). Transmission could be unidirectional or bidirectional and facilitated in response to a second stimulus train. We have shown that in chick or rat SS the NS-to-SGC leg of the two-synapse pathway is purinergic via P2Y2 receptors but the second SGC-to-NS synapse mechanism remained unknown. A noisy evoked current in the target neuron, a reversal potential close to 0 mV, and insensitivity to calcium scavengers or G protein block favored an ionotropic postsynaptic receptor. Selective block by D-2-amino-5-phosphonopentanoate (AP5) implicated glutamatergic transmission via N-methyl-d-aspartate receptors. This agent also blocked NS responses evoked by puff of UTP, a P2Y2 agonist, directly onto the SGC Cell, confirming its action at the second synapse of the SS transmission pathway. The N-methyl-d-aspartate receptor NR2B subunit was implicated by block of transmission with ifenprodil and by its immunocytochemical localization to the NS membrane, abutting the Glial septum P2Y2 receptor. Isolated DRG Cell clusters exhibited daisy-chain and branching NS-Glial Cell-NS contacts, suggestive of a network organization within the ganglion. The identification of the Glial-to-neuron transmitter and receptor combination provides further support for transGlial transmission and completes the DRG SS molecular transmission pathway.
Stacy E. Freeman - One of the best experts on this subject based on the ideXlab platform.
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Tonabersat Inhibits Trigeminal Ganglion Neuronal‐Satellite Glial Cell Signaling
Headache, 2009Co-Authors: Srikanth Damodaram, Srikanth Thalakoti, Stacy E. Freeman, Filip G. Garrett, Paul L. DurhamAbstract:Migraine patients often report sinus pressure or pain and nasal congestion during severe migraine attacks and it has been suggested that sinus pathology can act as a trigger of migraine.1,2 Furthermore, patients suffering from acute allergic rhinitis experience headache and migraine at a much higher frequency than nonallergic subjects.3 While migraine and rhinosinusitis exhibit considerable comorbidity, the underlying Cellular mechanisms are not well understood. However, it is well established that activation of trigeminal nerves and the peripheral and central release of neuropeptides are involved in mediating the inflammatory and nociceptive events characteristic of both migraine and rhinosinusitis.4–6 The trigeminal nerve consists of 3 major branches referred to as the ophthalmic (V1), maxillary (V2), and mandibular (V3) branches. Each branch provides somatosensory innervation of distinct regions of the head, face, nasal, and sinus cavities.7 Primary afferent neurons, whose Cell bodies reside in the trigeminal ganglion, convey sensory information from peripheral tissues implicated in migraine and rhinosinusitis to the central nervous system (CNS). The pathophysiological events involved in migraine and rhinosinusitis involve both peripheral and central sensitization.4,8–10 Peripheral sensitization, which is the result of increased activity of trigeminal nociceptors, is thought to play a key role in the initiation of migraine and rhinosinusitis, while central sensitization, which involves enhanced excitability of second-order neurons, leads to pain.11 Peripheral sensitization is characterized by increased neuronal excitability and a lowering of the threshold for activation. In this context, activation is defined as causing changes in the Cell that allow it to perform functions beyond those present in a basal state.12 It is now thought that glia Cells that are closely associated with peripheral and central neurons can directly modulate the functional and excitability state of these neurons.12,13 Furthermore, neuronglia interactions are reported to be involved in all stages of inflammation and pain associated with several CNS diseases.14,15 Within the trigeminal ganglion, the Cell bodies of neurons are completely surrounded by specialized Glial Cells known as Satellite glia that together form distinct, functional units.13 Morphological studies have provided evidence that neurons and Satellite Glial Cells extend processes that are thought to facilitate exchange of chemicals between neurons and glia.16,17 In addition, it was recently shown that trigeminal ganglion neurons and Satellite Glial Cells can communicate directly via gap junctions.18 Gap junctions serve as interCellular conduits that allow for direct transfer of small molecular weight molecules, such as ions, that regulate Cellular excitability, metabolic precursors, and second messengers.19,20 Gap junctions are found in most neurons and Glial Cells and function to facilitate neuron-neuron, glia-glia, and neuron-glia communication. Within the CNS, gap junctions are abundant and allow for extensive interCellular coupling between Cells that form a communication network.19,21 Each Cell contributes a hemichannel composed of 6 transmembrane proteins known as connexins. The connexin family includes more than 20 members.22 However, only 10 connexin proteins are known to be expressed by neuronal or Glial Cells.21 Connexins are dynamic membrane proteins that exhibit short half-lives.23 Changes in the expression of connexins and hence, communication through gap junctions, are associated with numerous CNS diseases including Alzheimer’s disease, as well as cortical spreading depression.19 Similarly, we have recently provided evidence of enhanced neuron to Satellite glia communication occurring through gap junctions within trigeminal ganglion in response to inflammatory stimuli.18 The expression of connexin proteins involved in forming gap junctions between neuronal and Satellite Glial Cells within the trigeminal ganglion under normal and disease states is not known. In addition, we have observed cross activation within the ganglion by which stimulation of neurons in one branch caused a rapid and sustained activation in the other branches, an example of intraganglionic communication.18 Based on our previous findings, we propose that neuronal-Satellite Glial Cell signaling is involved in initiating and maintaining peripheral sensitization within the ganglion and, thus, contributes to the significant comorbidity reported for migraine, acute sinusitis, and allergic rhinitis. In this study, we used an in vivo animal model to test whether treatment of V2 neurons by tumor necrosis factor-alpha (TNF-α), a cytokine whose levels are elevated in nasal secretions during allergic rhinitis, can reduce the amount of stimulus required for Cellular changes in neurons located in the V1 region, and thus act as a potential trigger. Increased neuron-Satellite glia communication via gap junctions, as well as increased levels of connexin 26 and active p38, was observed in neurons and glia located in both V1 and V2 regions in response to cotreatment with TNF-α and capsaicin. Another significant finding from our study was that pretreatment with the anti-migraine drug tonabersat decreased gap junction communication and the level of connexin 26, and blocked p38 activation in both neurons and Satellite glia.
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tonabersat inhibits trigeminal ganglion neuronal Satellite Glial Cell signaling
Headache, 2009Co-Authors: Srikanth Damodaram, Srikanth Thalakoti, Stacy E. Freeman, Filip G. Garrett, Paul L. DurhamAbstract:Migraine patients often report sinus pressure or pain and nasal congestion during severe migraine attacks and it has been suggested that sinus pathology can act as a trigger of migraine.1,2 Furthermore, patients suffering from acute allergic rhinitis experience headache and migraine at a much higher frequency than nonallergic subjects.3 While migraine and rhinosinusitis exhibit considerable comorbidity, the underlying Cellular mechanisms are not well understood. However, it is well established that activation of trigeminal nerves and the peripheral and central release of neuropeptides are involved in mediating the inflammatory and nociceptive events characteristic of both migraine and rhinosinusitis.4–6 The trigeminal nerve consists of 3 major branches referred to as the ophthalmic (V1), maxillary (V2), and mandibular (V3) branches. Each branch provides somatosensory innervation of distinct regions of the head, face, nasal, and sinus cavities.7 Primary afferent neurons, whose Cell bodies reside in the trigeminal ganglion, convey sensory information from peripheral tissues implicated in migraine and rhinosinusitis to the central nervous system (CNS). The pathophysiological events involved in migraine and rhinosinusitis involve both peripheral and central sensitization.4,8–10 Peripheral sensitization, which is the result of increased activity of trigeminal nociceptors, is thought to play a key role in the initiation of migraine and rhinosinusitis, while central sensitization, which involves enhanced excitability of second-order neurons, leads to pain.11 Peripheral sensitization is characterized by increased neuronal excitability and a lowering of the threshold for activation. In this context, activation is defined as causing changes in the Cell that allow it to perform functions beyond those present in a basal state.12 It is now thought that glia Cells that are closely associated with peripheral and central neurons can directly modulate the functional and excitability state of these neurons.12,13 Furthermore, neuronglia interactions are reported to be involved in all stages of inflammation and pain associated with several CNS diseases.14,15 Within the trigeminal ganglion, the Cell bodies of neurons are completely surrounded by specialized Glial Cells known as Satellite glia that together form distinct, functional units.13 Morphological studies have provided evidence that neurons and Satellite Glial Cells extend processes that are thought to facilitate exchange of chemicals between neurons and glia.16,17 In addition, it was recently shown that trigeminal ganglion neurons and Satellite Glial Cells can communicate directly via gap junctions.18 Gap junctions serve as interCellular conduits that allow for direct transfer of small molecular weight molecules, such as ions, that regulate Cellular excitability, metabolic precursors, and second messengers.19,20 Gap junctions are found in most neurons and Glial Cells and function to facilitate neuron-neuron, glia-glia, and neuron-glia communication. Within the CNS, gap junctions are abundant and allow for extensive interCellular coupling between Cells that form a communication network.19,21 Each Cell contributes a hemichannel composed of 6 transmembrane proteins known as connexins. The connexin family includes more than 20 members.22 However, only 10 connexin proteins are known to be expressed by neuronal or Glial Cells.21 Connexins are dynamic membrane proteins that exhibit short half-lives.23 Changes in the expression of connexins and hence, communication through gap junctions, are associated with numerous CNS diseases including Alzheimer’s disease, as well as cortical spreading depression.19 Similarly, we have recently provided evidence of enhanced neuron to Satellite glia communication occurring through gap junctions within trigeminal ganglion in response to inflammatory stimuli.18 The expression of connexin proteins involved in forming gap junctions between neuronal and Satellite Glial Cells within the trigeminal ganglion under normal and disease states is not known. In addition, we have observed cross activation within the ganglion by which stimulation of neurons in one branch caused a rapid and sustained activation in the other branches, an example of intraganglionic communication.18 Based on our previous findings, we propose that neuronal-Satellite Glial Cell signaling is involved in initiating and maintaining peripheral sensitization within the ganglion and, thus, contributes to the significant comorbidity reported for migraine, acute sinusitis, and allergic rhinitis. In this study, we used an in vivo animal model to test whether treatment of V2 neurons by tumor necrosis factor-alpha (TNF-α), a cytokine whose levels are elevated in nasal secretions during allergic rhinitis, can reduce the amount of stimulus required for Cellular changes in neurons located in the V1 region, and thus act as a potential trigger. Increased neuron-Satellite glia communication via gap junctions, as well as increased levels of connexin 26 and active p38, was observed in neurons and glia located in both V1 and V2 regions in response to cotreatment with TNF-α and capsaicin. Another significant finding from our study was that pretreatment with the anti-migraine drug tonabersat decreased gap junction communication and the level of connexin 26, and blocked p38 activation in both neurons and Satellite glia.
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Nitric oxide-proton stimulation of trigeminal ganglion neurons increases mitogen-activated protein kinase and phosphatase expression in neurons and Satellite Glial Cells.
Neuroscience, 2008Co-Authors: Stacy E. Freeman, Vinit V. Patil, Paul L. DurhamAbstract:Elevated nitric oxide (NO) and proton levels in synovial fluid are implicated in joint pathology. However, signaling pathways stimulated by these molecules that mediate inflammation and pain in the temporomandibular joint (TMJ) have not been investigated. The goal of this study was to determine the effect of NO-proton stimulation of rat trigeminal neurons on the in vivo expression of mitogen-activated protein kinases (MAPKs) and phosphatases (MKPs) in trigeminal ganglion neurons and Satellite Glial Cells. Low levels of the active MAPKs extraCellular signal-regulated kinase (ERK), Jun amino-terminal kinase (JNK), and p38 were localized in the cytosol of neurons and Satellite Glial Cells in unstimulated animals. However, increased levels of active ERK and p38, but not JNK, were detected in the cytosol and nucleus of V3 neurons and Satellite Glial Cells 15 min and 2 h following bilateral TMJ injections of an NO donor diluted in pH 5.5 medium. While ERK levels returned to near basal levels 24 h after stimulation, p38 levels remained significantly elevated. In contrast to MKP-2 and MKP-3 levels that were barely detectable in neurons or Satellite Glial Cells, MKP-1 staining was readily observed in Satellite Glial Cells in ganglia from unstimulated animals. However, neuronal and Satellite Glial Cell staining for MKP-1, MKP-2, and MKP-3 was significantly increased in response to NO-protons. Increased active ERK and p38 levels as well as elevated MKP levels were also detected in neurons and Satellite Glial Cells located in V2 and V1 regions of the ganglion. Our data provide evidence that NO-proton stimulation of V3 neurons results in temporal and spatial changes in expression of active ERK and p38 and MKPs in all regions of the ganglion. We propose that in trigeminal ganglia these Cellular events, which are involved in peripheral sensitization as well as control of inflammatory and nociceptive responses, may play a role in TMJ pathology.
